Copeland Sarah J, Thurston Susan F, Copeland John W
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Mol Biol Cell. 2016 Jan 15;27(2):260-76. doi: 10.1091/mbc.E15-02-0070. Epub 2015 Nov 12.
The Golgi apparatus is the central hub of intracellular trafficking and consists of tethered stacks of cis, medial, and trans cisternae. In mammalian cells, these cisternae are stitched together as a perinuclear Golgi ribbon, which is required for the establishment of cell polarity and normal subcellular organization. We previously identified FHDC1 (also known as INF1) as a unique microtubule-binding member of the formin family of cytoskeletal-remodeling proteins. We show here that endogenous FHDC1 regulates Golgi ribbon formation and has an apparent preferential association with the Golgi-derived microtubule network. Knockdown of FHDC1 expression results in defective Golgi assembly and suggests a role for FHDC1 in maintenance of the Golgi-derived microtubule network. Similarly, overexpression of FHDC1 induces dispersion of the Golgi ribbon into functional ministacks. This effect is independent of centrosome-derived microtubules and instead likely requires the interaction between the FHDC1 microtubule-binding domain and the Golgi-derived microtubule network. These effects also depend on the interaction between the FHDC1 FH2 domain and the actin cytoskeleton. Thus our results suggest that the coordination of actin and microtubule dynamics by FHDC1 is required for normal Golgi ribbon formation.
高尔基体是细胞内运输的中心枢纽，由顺面、中间和反面扁平囊堆叠而成。在哺乳动物细胞中，这些扁平囊被缝合在一起形成核周高尔基体带，这对于细胞极性的建立和正常的亚细胞组织是必需的。我们之前将FHDC1（也称为INF1）鉴定为细胞骨架重塑蛋白formin家族中一个独特的微管结合成员。我们在此表明，内源性FHDC1调节高尔基体带的形成，并与源自高尔基体的微管网络有明显的优先关联。敲低FHDC1表达会导致高尔基体组装缺陷，并提示FHDC1在维持源自高尔基体的微管网络中发挥作用。同样，FHDC1的过表达会导致高尔基体带分散成功能性小堆叠。这种效应独立于源自中心体的微管，相反可能需要FHDC1微管结合结构域与源自高尔基体的微管网络之间的相互作用。这些效应还取决于FHDC1的FH2结构域与肌动蛋白细胞骨架之间的相互作用。因此，我们的结果表明，FHDC1对肌动蛋白和微管动力学的协调对于正常高尔基体带的形成是必需的。
